Selective inhibitors of platelet lipoxygenase: 4,7,10,13-eicosatetraynoic acid and 5,8,11,14-henicosatetraynoic acid.
Nine acetylenic acids were evaluated to determine what structural features are required for selective inhibition of platelet lipoxygenase. Both 4,7,10,13-icosatetraynoic acid and 5,8,11,14-henicosatetraynoic acid inhibited the synthesis of 12-L-hydroxy-5,8,10,14-icosatetraenoic acid (HETE) more than 95 percent without significantly altering the production of either thromboxane B2 or 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT). The ID50 concentrations (microM) for inhibiting the synthesis of thromboxane B2 and HETE were respectively 51 and 0.46 with 4,7,10,13-icosatetraynoic acid while similar concentrations of 64 and 0.31 were found for 5,8,11,14-henicosatetraynoic acid.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000096:biosynthesis; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D016859:Lipoxygenase Inhibitors; D013329:Structure-Activity Relationship; D013929:Thromboxane B2 / Q000096:biosynthesis
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D016859:Lipoxygenase Inhibitors; D015117:5,8,11,14-Eicosatetraynoic Acid; C029511:5,8,11,14-heneicosatetraynoic acid; D013929:Thromboxane B2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C029510:4,7,10,13-eicosatetraynoic acid